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Maternal Programming of Defensive Responses 153One critical question concerns the potential consequences of these differencesin maternal behavior for the development of behavioral and neuroendocrine responsesto stress (Caldji et al., 1998; Liu et al., 1997; Weaver et al., 2004a,b). Asadults, the offspring of High LG-ABN mothers show reduced plasma ACTH andcorticosterone responses to acute stress by comparison to the adult offspring ofLow LG-ABN mothers. As mentioned above, circulating glucocorticoids regulateHPA activity in corticolimbic structures, such as the hippocampus. High LG-ABN offspring show significantly increased expression of genes that controlhippocampal glucocorticoid receptors, enhanced glucocorticoid negative feedbacksensitivity and decreased hypothalamic CRH mRNA levels. Moreover, Liu et al.(1997) found that the magnitude of the corticosterone response to acute stress wassignificantly correlated with the frequency of both maternal LG (r = -.61) and ABN(r = -0.64) during the first week of life, as was the level of hippocampal glucocorticoidreceptor mRNA and hypothalamic CRH mRNA expression (all r’s > 0.70).The offspring of the High and Low LG-ABN mothers also differ in behavioralresponses to novelty (Caldji et al., 1998; Francis et al., 1999). As adults, the offspringof the High LG-ABN mothers show decreased startle responses, increasedopen-field exploration, and shorter latencies to eat food provided in a novel environment.The offspring of Low LG-ABN mothers also show greater burying inthe defensive burying paradigm (Menard et al., 2005), which involves an activeresponse to a threat. The offspring of the High LG-ABN mothers also show decreasedCRF receptor levels in the locus coeruleus and increased GABA A /BZreceptor levels in the basolateral and central nucleus of the amygdala, as well asin the locus coeruleus (Caldji et al., 1998, 2003) and decreased CRF mRNA expressionin the central nucleus of the amygdala. Note that BZ agonists suppressCRF expression in the amygdala (Owens et al., 2001). Predictably, stress-inducedincreases in PVNh levels of noradrenaline that are normally stimulated by CRFwere significantly higher in the offspring of the Low LG-ABN offspring (Caldjiet al., 1999).Effects of Maternal Care on Genetic ExpressionMaternal care during the first week of life is associated with stable individualdifferences in the expression of genes in brain regions that regulate stress reactivity.The adult offspring of High LG-ABN mothers show significantly higher levelsof GABA A /BZ receptor binding in the basolateral and central nuclei of the amygdalaas well as the locus coeruleus. These findings provide a mechanism for increasedGABAergic inhibition of amygdala-locus coeruleus activity. A series of in situhybridization studies (Caldji et al., 2003) illustrate the molecular mechanism forthese differences in receptor binding and suggest that variations in maternal caremight actually permanently alter the subunit composition of the GABA A receptor